Citric Acid Inhibits Fermentation

Background:

Citric acid exists in large amounts in a variety of fruits and vegetables, most notably citrus fruits and was first time isolated from lemon juice. Its salt form, Citrate, is an intermediate in the citric acid cycle (also called TCA cycle, TriCarboxylic Acid cycle, Krebs cycle, Szent-Györgyi – Krebs cycle), a central metabolic pathway for animals, plants and bacteria.

In others words, Citrate is a major product of mitochondria, the engine of the cell. When there is to much Citrate going out of the engine, it means there is enough energy produced by the engine and a feedback mechanism will “talk” to the glycolisis (Ref.), the path through which fuel is provided to the engine, and ask to reduce the amount of fuel. As a result, the more Citrate builds up in the cell, the more the cell will think it has enough of what it needs and will reduce or even shut down the glycolisis process.

Since glycolisis (or fermentation) is essential in most cancers to obtain various elements required for the survival of the cancer cells (e.g. fast energy production, anti-oxidants, etc.), glycolisis inhibition may directly lead to the eradication of cancer cells. Inhibiting glycolisis will also lead to a lower amount of acidity produced and exported by the cancer cells and thus a better tumor environment in which the immune system (T cells) will reactivate (Ref.) or chemo therapies can go through without being deactivated (protonated). From this point of view, I would expect that Citrate can both work alone but also enhance chemo therapy (Ref.) and immunotheraphy.

From a scientific point of view, the inhibitory effect of glycolisis triggered by Citrate is well understood and recognized (see references in the Mechanism section and Reference section). So there is no question about that. This is why Citrate has been indeed proposed as an anti cancer agent. However, the questions is whether the same theoretical and laboratory results can be achieved in humans.

Interestingly, Dr. Alberto Halabe Bucay in Mexico, was one of the few proposing and using Citric Acid to treat and cure cancer patients so far. While Dr. Alberto reports are typically very short, of anecdotal stile, the results emerging out of that indicate that in some advanced cancer patients Citric Acid used as stand alone therapy may lead to tumor regression in patients with various tumor types. His number of published case reports is truly impressive to me. Yet, it is a pitty to see the anecdotal stile of the published reports as they are difficult to judge. Here is Dr. Alberto’s Twitter account where he is constantly sharing links to new published successful cases: https://twitter.com/Cancercuretop2, and here is the Facebook page https://www.facebook.com/alberto.halabebucay

Off course, the questions that remains open to me is how many patients were treated with Citric Acid to get to those successful cases reported.

Update 25-02-2017: If Dr. Alberto would be the only one to claim curing cancer patients with Citric Acid, the story would not stand so strong and more evidence would be required. However, one of the contributors on this website (thank you Dr. Helga) has recently pointed out that Citric Acid has been used successfully against cancer since 1866 and reported at that time in the respectable scientific journal “British Medical Journal” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2309166/pdf/brmedj05661-0005.pdf

So what we have here is an element that is cheap, safe, easy to administrate (orally), accessible, with clear theory regarding the anti cancer mechanism and as Dr. Alberto Halabe Bucay and those before him demonstrated, relevant in various types of tumors.

However, it is my personal opinion that Citric Acid comes with a risk as well. This is just my theory, and that is due to the fact that it may also represent a fuel for cancer cells out of which some cancer cells may produce cholesterol, much needed for fast cellular division and hormone production. To reduce or eliminate this risk, as discussed below, I would always combine Citric Acid with a Statin and HCA. These drugs/supplements will not only reduce this risk but also are drugs/supplements with well known anti cancer effect as well.

Funny enough, while writing the end of this article I realize it now makes scientific sense to drink lemon juice in order to kill cancer (see the estimations on how much lemon juice or grapefruit juice we would need to drink daily, in the Source section of this post). I never believed this is possible before, but now, based on all these references and mathematics, it makes sense. Note: Lemonade therapy is also suggested / used in hospitals as a therapy to address kidney stone formation / nephrolithiasis (Ref.1, Ref.2, Ref.3)

Results in Humans:

There are various case reports, nearly all from Dr. Halabe, indicating Citric Acid is effective against various forms of cancer, in humans:

Therefore, the wide effectiveness of Citric Acid against various forms of cancer has still to be demonstrated by sources other than Dr. Halabe.

Mechanism:

Citrate is a key intermediate in both catabolism and anabolism and occupies a prominent position in cell energy metabolism. There are two sources of intracellular citrate:

1. Citrate is produced inside the mitochondria within the Krebs cycle. When the cell has excess energy, citrate is transported out of the mitochondrial matrix across the inner membrane via the mitochondrial citrate transport protein (CTP). In the cytoplasm, is then broken down by the ACLY (ACL) enzyme into

High concentrations of cytosolic citrate can inhibit phosphofructokinase, one of the most important control “knob” in the mammalian glycolytic pathway. A high level of citrate means that biosynthetic precursors are abundant and additional glucose should not be degraded for this purpose (Ref.)

Therefore, high concentrations of citrate will inhibit the conversion of fructose 6-phosphate, into its next step in glycolysis, i.e. fructose 2,6-bisphosphate (F-2,6-BP).

Interestingly, a fall in pH also inhibits phosphofructokinase activity (Ref.) representing a link between the cancer treatment strategy focused on cancer cell acidification I discussed in another post (Ref.) and glycolisis inhibition.

Obviously, the inhibition of glycolisis is highly relevant in cancer cells and it can lead to cancer cell death. Indeed this fact has been demonstrated in several papers (please see the Reference section).

2. Citrate is not only produced by mitochondria but can also be taken up from blood through PMCT plasma membrane transporters (Ref.) or the so called NaCT (Ref.). Because NaCT is more activated in the acidic environments (Ref.1, Ref.2), cancer cells may absorb higher levels of Citrate compared to normal cells.

As a side note, Prostate gland, is known to produce and release large amounts of citrate during its normal secretory function. (Ref.) This may be a reason why not to use Citric Acid for prostate cancer and possibly other cancers of hormone producing cells.

Other anti cancer effects of Citrate may be related with its capability to promote acetylation of histones, to inhibit tumor angiogenesis and other potential mechanism (Ref.)

Citrate also causes anticoagulation by chelation of calcium, and is likely to lead to magnesium chelation as well. (Ref.)

Update 30-March-2017:

Citric Acid seems to also inhibit pyruvate dehydrogenase (PDH): “Citrate inhibits the interconversion of the inactive form of pyruvate dehydrogenase to the active form of the enzyme.” (Ref.) I did not know this, and if this is true, Citrate should not be used with DCA since the whole point of DCA is to re activate PDH by inhibiting PDK https://www.cancertreatmentsresearch.com/dichloroacetate-dca-treatment-strategy/

In other words, if the results presented in this paper are true, when using Citrate + DCA we may need to make a choice between the use of DCA and that of Citrate since DCA will try to activate PDH while Citrate will inhibit PDH. If Citrate indeed inhibits PDH, I expect Citrate will win the fight since it may act directly on PDH while DCA acts indirectly through PDK.

The inhibition of PDH and Citrate Synthase by Citrate, indicates that Citrate may not only interfere with glycolisis but also mitochondria function in cancer cells.

Dose & Administration:

Although there are publications suggesting sodium citrate as an anti cancer element too, Dr. Alberto insists in using Citric Acid only as that was clearly demonstrated to be effective.

The daily dose seems to be min 4g/day and up to 30g/day. Yet 4g to 8g/day seems the most common dose used by Dr. Alberto.

It has been claimed to be completely safe. It is recommend to be combined with juices or meals (as powder or capsules) and also it is recommend to be taken with antacids like omeprazole prior to the administration of Citric Acid (in order to increase Citric Acid absorption in the body). (Ref.1)

Start with 500mg 3x/day and move up to the target dose of for example 10g/day.

Some more ideas for its application:

In order not to have Citrate converted to acetyl-CoA, and also to build up faster Citrate in the cytosol, inhibit ACYL with HCA(https://www.cancertreatmentsresearch.com/?p=956). That means, it may be wise to add HCA capsules (1. to 3 g/day) during Citrate administration.

In case Citrate is still converted to acetyl-CoA even if HCA is used, use Statins(FDA approved drugs) to inhibit further cholesterol production

It may also be wise to target and slow down mitochondria during Citrate administration with e.g. Metformin, Doxycicline, etc.

Update 25-02-2017: Interesting enough, it has previously suggested that DCA, another well known anticancer drug, can induce the accumulation of high level of citrate inside the cytoplasm and with that inhibit glycolisis (Ref.). Therefore, a good addition to the Citric Acid treatment may be DCA.

Update 30-March-2017: According to additional info I came across and shared as an update in the “Mechanism” section, it doesn’t make sense to add DCA to Citric acid since DCA will try to reactivate PDH while Citric acid will inhibit that. Therefore, based on the latest info, I would not use CA+DCA at the same time but try one for longer time, if I would see progression I would switch to the other. So maybe one month try and observe the markers?

Actually, if I think more, due to the ACLY over activation in many cancers (Ref.), I would not take Citrate without inhibiting Citrate conversion to acetyl-CoA with ACLY inhibitors. Therefore, I would always use HCA supplements when on Citrate therapy.I would also use a Statin (preferably lipophilic) to make sure the cholesterol production will be limited while on CA.Specifically, hormone producing cells such as prostate cells are very capable to convert Citrate into acetyl-CoA as they typically have to do that in order to obtain the cholesterol required for hormone production (Ref.). Note: I read somewhere that Metformin may also downregulate ACLY but cannot find the reference right now.

Because Citarte is transported inside the cells by a Na coupled transporter (Ref.), I guess table salt may enhance Citrate absorption.

Update 27-02-2017: Ergin, one of the contributors on this website, has recently pointed out a relevant paper http://file.scirp.org/Html/6-2700957_37559.htm This paper suggest (but is not totally clear) that CA may boost gluconeogenesis (that is different than glycolisis) leading to a high glucose level in the blood. If this is true, it is something we do not want. So what we can do about it?
First, anyone who is using CA can measure his blood glucose levels using a typical measurement toll that can be used to measure glucose at home. If indeed, the glucose levels are increasing after CA, what I would do is to always use Metformin before CA administration. That is because Metformin is an inhibitor of the gluconeogenesis.

As a result of our discussions so far, to address the potential weak spots of CA treatment, I would combine CA treatment with Metformin (500mg) and HCA (500-1000mg) (both ingested about 30 min prior to taking CA). Metformin would address potential increase of gluconeogenesis by CA, and HCA will address potential conversion of CA in cholesterol and other fuels for cancer via the potentially upregulated mevalonate pathway as previously discussed.

There is a good amount of scientific evidence suggesting that both HCA and Metformin have good potential against cancer. As a result, including the two will only increase the chance of success.

Update 28-02-2017: Following our discussion on the potential increase in blood glucose level after taking CA, I did check if there is any such increase in my case. I mixed 4g of CA with water and took that at once. Measured blood glucose once before taking CA and a few times after, at 5min, 30min and one hour. During this time, there was no specific increase of the blood glucose.
This may be specific to my case, so others may want to check for themselves, but these results are not supporting the claims in the article http://file.scirp.org/Html/6-2700957_37559.htm Yet, everyone should check this for himself. Based on this result, Metformin would not be necessarily required when using CA but I would probably use it anyway given its important benefits in cancer.

Indeed pentose phosphate pathway (PPP) is very relevant in cancer and inhibition of glyco may redirect glucose and in turn fuel PPP. And as explained here “PPP is especially critical for cancer cells because it generates not only pentose phosphates to supply their high rate of nucleic acid synthesis, but also provides NADPH, which is required for both the synthesis of fatty acids and cell survival under stress conditions.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329227/
Therefore, if we inhibit glycolisis after G6P (see https://www.cancertreatmentsresearch.com/acetate-fuels-cancer/), which is what CA may do, we also need to make sure we inhibit or reduce PPP or alternatively the activity of mithocondria (with e.g. Metformin) which otherwise will switch on fatty acids.

Interestingly, PPP can be reduced/inhibited by DHEA, which seems to inhibit glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway. DHEA can be found as a supplement online http://www.webmd.com/diet/dhea-supplements#1

BUT, we need to be careful because as the reference above states, “in contrast to the expected resistance exerted by the elevated PPP in response to certain drugs, the PPP may sensitize cells to other therapeutic drugs. Indeed, it appears that the high levels of NADPH generated by a hyperactive PPP sensitize cells to anthracyclines. Anthracyclines are a class of antibiotics used in cancer therapy, and the most commonly used member of this class is adriamycin, also known as doxorubicin. Anthracyclines are metabolized by cytochrome p450 reductase to produce free radicals, which induce cytotoxicity72. Because NADPH is a cofactor that is required for this activity of cytochrome p450, the high levels of NADPH generated by the PPP may sensitize cancer cells to doxorubicin”.

In summary:
– CA may lead to increased activity of PPP
– PPP is relevant in cancer and its inhibition may help fighting cancer
– PPP may be inhibited by DHEA, which can be found as a supplement online
– some tumors (such as adrenocortical carcinoma) naturally produce high levels of intracellular DHEA, inhibiting PPP
– but active PPP may help some specific chemos such as doxorubicin – therefore CA during doxorubicin may be beneficial

Large doses may cause hyperkalemia and alkalosis, especially in the presence of renal disease. Concurrent administration of potassium-containing medication, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, or cardiac glycosides may lead to toxicity. (Ref.)

Academic investigations are currently running focused on limiting absorption of Citrate as this approach might mimic caloric restriction, decrease fatty acid and cholesterol biosyntheses, prevent obesity, and extend life-span (Ref.). Consequently, long term use of Citric Acid may be detrimental.

So based on the above it seems that in order to ingest e.g. 10g of citric acid/day we need to drink about 250ml lemon juice. This seems feasible to me and offcourse, I would drink this mixed with water during one day. Alternatively, I would drink about 500ml of grapefruit juice daily, which I think is very easy to achieve. What is not clear to be yet is the bio availability difference between using the fruit as a source or the commercially available powder.

Funny enough, I now realize that with this article and the enclosed references it now makes scientific sense to drink lemon juice in order to kill cancer. I never believed this is possible before, but now, based on all these references and mathematics, it makes sense. 🙂

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention.

Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

In this article, I present the hypothesis that cancer presents due to the domination of the cell by mitochondria, which, from an evolution viewpoint, appeared in multi-cellular living being with the incorporation of a bacteria into a primitive cell, the bacteria sustained itself as mitochondria and these conserved their identity and bacterial characteristics, based on this, the hypothesis is suggested of the biological competition between the cell and the mitochondria; the mitochondria, on establishing itself as an independent entity within the cell, created the need to permanently remain in the cytoplasm of the cell, thus, from an energy viewpoint, when a cell becomes malignant, the mitochondria are the sole beneficiaries, as there is an ideal environment at the cellular level for the mitochondria to sustain their functions, and from this hypothesis, the treatment for fighting cancer consists of inhibiting glycolysis, being the principal source of energy for the mitochondria, this is achieved by administering citrate to cancer patients, as the citrate inhibits the phosphofructokinase enzyme, the pyruvate dehydrogenase complex and the succinate dehydrogenase enzyme of Krebs cycle, thus, the mitochondria will be forced to limit their metabolism and, secondarily, will lower the reproduction capacity of the cell in general.

The inhibition of two major anti-apoptotic proteins, Bcl-xL and Mcl-1, appears essential to destroy chemoresistant cancer cells. We have studied their concomitant inhibition, using ABT 737 or siRNA targeting XL1 and citrate, a molecule which reduces the expression level of Mcl-1.Two cisplatin-chemoresistant ovarian cell lines (SKOV3 and IGROV1-R10) were exposed to ABT 737 or siRNA targeting XL1 and citrate at various individual concentrations, or combined. Cell proliferation, cell cycle repartition and nuclear staining with DAPI were recorded. Western blot analyses were performed to detect various proteins implied in apoptotic cell death pathways.Mcl-1 expression was barely reduced when cells were exposed to citrate alone, whereas a mild reduction was observed after ABT 737 treatment. Concomitant inhibition of Bcl-xL and Mcl-1 using ABT 737 or siXL1 associated with citrate was far more effective in inhibiting cell proliferation and inducing cell death than treatment alone.Given that few, if any, specific inhibitors of Mcl-1 are currently available, anti-glycolytic agents such as citrate could be tested in association with synthetic inhibitors of Bcl-xL.

Gastric carcinoma is frequent, particularly in China, and therapy is often inefficient. Because cancer cells are partly or mainly dependent on glycolysis to generate adenosine triphosphate ATP (Warburg effect) and/or to produce precursors (of lipid, nucleotides, etc.) for building new cells, any inhibition of glycolysis may slow down the cell proliferation and/or may kill cells. The antitumor effect of citrate, an anti-glycolytic agent inhibiting phosphofructokinase (PFK) was tested on two human gastric carcinoma cell lines. Materials and Methods: Cell viability and morphology were assessed after 24-72 h exposure to citrate (5, 10, 220 mM). Apoptosis was assessed by annexin V-FITC/PI staining and Western immunobloting. Results: A 3-day continuous exposure to citrate led to near destruction of the cell population in both cell lines, apoptotic cell death occurred through the mitochondrial pathway in a dose- and time-dependent manner, associated with the reduction of the anti-apoptotic Mcl-1 protein in both lines. Conclusion: Citrate demonstrates strong cytotoxic activity against two gastric cancer lines, leading to an early diminution of expression of Mcl-1 and to massive apoptotic cell death involving the mitochondrial pathway.

Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy. Strategies aiming to increase cytosolic citrate should be developed and tested in humans, knowing that experimental studies have shown that administration of citrate and/or inhibition of ACLY arrest tumor growth, inhibit the expression of the key anti-apoptotic factor Mcl-1, reverse cell dedifferentiation and increase sensibility to cisplatin.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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1. I published that citric acid cures cancer, not lemon or grape juice, the citric acid in fruits doesn’t have the same effect.

2. My articles are not short, they are consecutive to my work published since March, 2007, the first time published in History that citric acid (citrate) is effective as a Cancer treatment. In the articles cited here my articles are part of their references.

3. Don’t get confused, my work is described in 8 simple words: Citric acid is effective as a Cancer treatment.

Dear Dr. Alberto, thank you for your comment. Can you please let me know what is in your view the reason why Citric Acid in fruits is not leading to the same anti cancer effect compared to the citric acid administrated as a supplement, assuming we take them in the same quantity? Is this opinion based on theoretical mechanisms, or based on your personal observation in patients? Any reference to support this view would help.

Thank you. I understand that you are questioning the bio availability of citric acid in the fruits including Lemon. I will search and see if I find anything on that so that we have a clear number on its bio availability.

Regarding the daily ingestion of citric acid from fruits, I am not sure how that is in other regions, but in Europe people are far from drinking 500ml of grapefruit juice or 250ml of lemon juice every day. I personally tried to drink every morning 250ml of grapefruit juice and it was challenging to do that every day.

Nevertheless, I would agree with the following: since you have seen that citric acid supplementation as powder or capsules can (in some cases?) lead to cancer suppression it may be best for the patient to start with that instead of the fruits. If however, a patient would not want to take all that citric acid as powder or capsule, the other option is to try the lemon juice or others.

One last note: As discussed in the post above, I strongly believe that HCA supplements added to the Citric Acid therapy will lead to improved success rate as it reduces the conversion of Citrate to acetyl-CoA (by inhibiting ACLY).

All right, Daniel, Thanks to God we live in a free World, so you can beleive anything you want, just consider that those compounds may be toxic… and that is published that citric acid “alone” cures cancer, scientifically in 25 consecutive articles…

While I very much appreciate your work and contribution to society, I do believe it would be very constructive to inhibit ACLY during Citric Acid administration, specifically in those cancer recognized to have high ACLY expression. (these cancer know very well how to handle Citrate and they may otherwise use Citrate for their own benefit instead).

Yes, and, consider, that the possibility that large number of patients with cancer worldwide are taking citric acid, without notification, and improving, is very high, including the President Jimmy Carter:

Indeed, but that is difficult to judge objectively. In order to get to the citric acid dose required for the anti cancer action which you demonstrated, people have to specifically target that. On this line, I think very few would just take that high amount of citric acid by chance as they need to do make an effort to get to the required dose. I do know a patient taking sodium citrate in high dose (but I think you do not agree with using sodium citrate as a solution?).
Based on my “statistics” so far, very few are taking pure citric acid but possibly many are drinking high dose citric juices that may help them to get to the required daily dose. While the news are claiming President Jimmy Carter was cured by anti PD1 drugs, it is possible that those well informed like him may have been cured with other substances such as citric acid. But off course we will never know that and it is difficult to argue one way or another.

Dr: Halabe
I would like to communicate with you regarding your protocol . I am a doctor here in California and would like to also invite you to a radio program to interview you for Spanish radio here. There are so many patients in this community that don’t know about these alternatives ..
drT

Thank you Emad! I so much like to have some statistics too. But I also understand that in reality it is difficult to track and get any statics out of that, being one Dr. only and not knowing what is the patient compliance, etc. This is why I didn’t ask anything on this line.

Hi Pouya. Due to its mechanism of action (inhibition of PFK), Citrate is a glycolisis inhibitor. In my view, all glycolisis inhibitors (some more than others) are enforcing a higher rate of energy (ATP) production in mitochondria which is well known to lead to ROS generation. Assuming this is true, Citrate anti cancer effects are pro-oxidant.

Daniel, I am busy to read all your blog and I would like to tell you how impressed I am about your job. I still do not understand many things, ( I believe you have to be scientist for that) but I am learning something everyday. Are there any things which would counteract citric acid? I really want to believe that it works and we are busy with it. Just wonder, but it is a question to dr Halabe, if there are any people with cancer who didn’t respond?

Hi Ann, thank you. I guess there are people who respond and people who are not responding. We do not have any statistics available but like with all potential treatments it also very much depends on the dynamics of the specific substance in each patient. In our case, in order to increase the chance of success, we are trying to add more treatments (such as Citrate) that are working in the same direction and not opposite to each other.

In that case you may need to add more magnesium or make a choice if it makes sense to use citrate or better magnesium, Ann. Can you please send me the reference on how magnesium helps fighting cachexia? Thank you.

Hi Ann, can you please register as an user? Otherwise I have to approve each comment you add. If you are an user I just approve once and than all the other comments will be published directly with no need for my approval.
Thank you for the link. They do not explain the mechanism behind Mg anti cachexia – I will check if there is anything real when I have time.
Citrate doesn’t have to reach mito but cytoplasm. I am not sure what will happen if there is a large amount of Mg supplementation in a patient that takes Citrate. Just search the literature and see what you can find on that. Now I go to sleep 🙂

And question number two :
If we will supplement with citric acid to stop or reduce glycolysis, will cancer switch to another way to produce energy/to grow/ to survive – in that case should be try to do something more if only citric acid will not help?

Hi Ann, very good question in my opinion. This is what I thought too so I wrote in the post above that I would combine Citrate with mitochondria targeting elements such as Metformin, Doxycicline, etc.
Just in case we are dealing with cancer cells able to convert higher levels of Citrate fast to acetyl-CoA, I would use HCA always and possibly statins.

Dear Daniel,
Could Paw Paw be beneficial, or Graviola? Or something else.
Inhibition of fermentation with CA is very interesting, but what about the /other/ part of it’s metabolism?
Beyond Warburg http://www.nature.com/articles/srep04927
It may be that you already know about that article. Ann is asking the right question i believe. RO power LOL.

I hope you are not in pain, if so, does Citric Acid help?
Looking forward to find out more about your condition and treatment.
Anything you would recommend? All i managed to try with my mother with some modest results are Aspirin+CBD oil.
But the aspirin dosage was toooo much to mentain. If only there was some solution to the side effects of aspirin, truly it would be a miracle cure, i believe. At least for many. But now i look forward to see how Citric Acid works for my mother.
Thanks to Daniel and those who contribute, we now have the chance to try some of the things talked about here.
I’m in a terrible financial pit, just like so many of us are in RO/TR but i soon hope to be able to afford to get more treatment items for my mother.
I made efforts to get Paw Paw and Graviola for my mother, in hope that it will be “THE CURE” as promised by so many.
Most likely it did not work since markers almost doubled in 20 days of use.
I still hope the entire effort was not in vain and that it may still prove to be something good to add.

Should the daily diet be considered when using the citric acid treatment, eg. Sugar, alcohol and red meat tend to make the blood more acid, in which environment cancer thrives, while cancer should not thrive in a blood level of pH 7,4. So if you have a big intake of sugar you would decrease the influence of citric acid?

The elements in the diet you mentioned are those that should be eliminated by all cancer patients in my view. Or at least no sugar and reduced red meat and alcohol. Also, I would always try to reduce the acidic balance in cancer patients. I previously discussed pH lowering strategies here https://www.cancertreatmentsresearch.com/?p=1178. Actually, citrate should be able to reduce that since it may inhibit glycolisis and as a result lactic acid production.
Regarding the effectiveness of Citrate as a function of the blood pH, I do not have a reference on that.

Citric acid is also a common food additive because it has a sour flavor and is used as a flavoring agent. You take up citric acid that you consume into the bloodstream, but most of it simply passes from there into your urine and is excreted from the body.

Cellular Uptake
A small amount of the citric acid you consume gets taken up by cells — mainly liver cells — explains K. Inoue and colleagues in a 2002 study published in “Biochemical and Biophysical Research Communications.” When your cells take up citrate, they can convert it to fat. While this sounds like a bad thing, only a very small amount of the citrate you consume ever ends up in the cells, so the effect is minimal.

We still give it a try, but I am not sure if we can really have something from it.

Here are references suggesting that citric acid absorption is fast and can lead to high serum citrate: “Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load.” http://www.ncbi.nlm.nih.gov/pubmed/1552616

And here is an even more clear reference “Fegan and associates,35 using an intestinal washout technique, reported 96% to 98% absorption of an oral citrate load within 3 hours in both stone-forming and normal subjects. Others have demonstrated a significant increase in serum citrate after an oral citrate load.36” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777061/

Thank you Paul. Very good point indeed. I know some of the authors personally and also cited them in some of the other posts. Indeed, they had good results with that combination and I would expect that adding Citrate to that would accelerate the cancer cell death. Offcourse we can argue that if some of the cancer cells are relying on mito, than those would survive to this strategy and only HCA may stay (a bit) in their way. So the “perfect” combination on this line may be ALA (or DCA) + HCA + Citrate +Ibuprofen + Metformin + Doxycicline + Pyrvinium Pamoate + Salinomycin + Meclizine. ALA or DCA pushes pyruvate in mitho, HCA leads to accumulation of Citrate, Citrate adds to that to inhibit Glyco, Ibuprofen (or other MCT4) inhibitors would lower the option of lactate to be pushed out of the cell in case that is still produced. All the others will target mito via different mechanisms.

Would you be nice and give more information about dosage and timing for this “perfect” combo?
With or without food, combinations in one administration if any.
I’m sure everyone would appreciate to have a page where we list the best strategy in theory or practice even.
In the end i feel we must come to some conclusions, what works and what doesn’t an overall thing. I’m sure you understand.
Some kind of general protocol.

Take care, don’t forget about your health Daniel. We need you! We must complete the project and i wish to join you ASAP.
Thank you!

Oh,then only two ingredients are missing to the perfect combination in our home treatment Doxycycline and Salinomycin. Salinomycin is the difficult one to buy, found 99.9% purity for $5/g on Alibaba.The question is if they want to sell to private customers.
You are great help Daniel,thank you.

Thanks Paul. For Salinomycin I would go to a professional clinic and certainly would not buy from Alibaba. There is no way 99.9% Sal would be 5USD/g, not even from China. (Note: I did spend time to find a good and high purity Sal source in China and would suggest not to spend your time with that).

I just read about a late t which talks about inhibition of anaerobic glucose metabolism for cancer treatment. However, it is too technical for me to understand. If you can have a look and see if in your opinion it would be effective and is this compound available online. Here’s the link http://www.google.com/patents/WO2006017494A2?cl=en

hello guys I can’t post as registered user.why??
Anyway..Hello, I didn’t know anything about citric acid and cancer.Dr Alberto is the first one who developed CA as effective anticancer protocol, no question about it. I don’t know about the eficacy but Dr says it is the cure..I believe him, he is working with it for 27 years, and the published case reports show this.My father 64 yo has metastatic gastric cancer in liver and peritoneum.Had chemo with little to zero results.Now he had jejunostomy because he could swallow and after this he developed edema and ascites. Albumin level is low…The doctors told us that he has maybe less than a month to live.He is really bad..I started giving him about 6 grams citric acid five days ago, nothing to report, it is too early, but it is our last hope. I will let you know.
question: I give him 1 gram in the morning 4 grams at noon and 1 gram at night. Do I have to split the dose accurately 2 grams/3 times daily?

hi kos, OK so that doesn’t help. if you want to try this route, I would make sure I add HCA next to Citrate and DCA if possible. Metformin if possible – this is my opinion. HCA is easy to order from iHerb and will arrive in less then a week. DCA from https://www.dcalab.com/ Metformin from the pharmacy if your doctor is willing to help. This is what I would do, but you have to think what is best for your needs.

As an aside: in some countries, Metformin is available without a prescription (or maybe the regulatory bodies in the nation’s are relaxed). In Bosnia, I was able to just ask for it at a pharmacy and was given as many boxes of it as I could carry. If you have family or friends in some lesser developed countries, you might be able to obtain it without a physician’s help.

Thank you for your interest Daniel and Meech. I appreciate your help. I can’t give him HCA and Metformin right now. He lost much weight in one month, he couldn’t eat anything for 14 days and then he had surgery…after this he couldn’t eat more than 900 kcals a day because intestines have to reprogrammed…Our shortly goal is to make him consume 1800-2000 kcals per day with high protein level. It is too risky to add HCA or/and Metformin in this stage.Luckily we are from Greece and can obtain Metformin. Tomorrow I’m going to add Alpha Lipoic Acid to the regimen.
Daniel, how DCA will help? I’m having a terrible migraine headache, due to lack of sleep and I can’t search on my pc.
Thank you.

Hi Kos, ALA will do the same as DCA but better to use DCA when is available. DCA will facilitate the move of pyruvate in to the mitochondria so that ther ewill be more Citrate created out of Glucose. Citric Acid will further increase the cytosolic level of Citrate. HCA will lower the chance that Citrate is converted in cholesterol or fatty acids so that there is an enhanced accumulation of Citrate. Metformin help in many ways. That is the theory.

A very simple way to add calories are oils and fats. Since I’m on a ketogenic diet I have trouble meeting caloric goals, so what I do is make a daily smoothie:

-A handful of raspberries
-2 TBSP olive oil
-2 TBSP flaxseed oil
-1 TBSP coconut oil (too much of this can cause diarrhea and stomach upset so maybe even 1 TSP)
-2 TBSP peanut butter
Macadamia/coconut/hazelnut/almond -Milk or water (if water, you’ll have to constantly stir since oils and water do not mix and the constituents will separate)

Then mix it in a blender. This is around 800 kcal in one drink 2 which comes out to about 500mL.

Oils and nuts are loaded with healthy fats and are high in calories. Best of luck.

So we had control today, and tumors grew unfortuantely, bilirubine is decreased ( oeuf), there is no more situataion which I would call ‘life in danger’. I must say that in the last two weeks I didn’t use anything, because we were all scared that Freddy will not make it. But apparently liver is recuperating little by little.
Freddy will be put under chemo FOLFIRI plus Avastin, for some time, to let the sickness under control and then we will think about TACE. For the moment TACE is too dangerous.
I want to come back to something as treatment.
I want to use HCA, Citric acid , DCA and metformin plus Quercetin .
But question about DCA -as this can be toxic to liver ( and I do not want to add something in plus, as next week Folfiri will surely damage a lot in liver) is it better maybe to use ALA – it help regenerate liver I think.
And later, is DCA compatible with FOLIRI?

Thanks Daniel.
I use also Essentiale forte, it works very good for liver.
But about hepa-merz – it helps to reduce ammonia. So if level of ammonia is ok in the blood, is there need to use it? Does it addres any other problems of liver?

I have a silly question. In most of studies are using citrate salts, not citric acid and find this citrate (anion?) as drastic agent against tumors. Citric acid comes to market as anhydrous or monohydrate but manufactures don’t mention which form are selling, at least in Greece. So when citric acid dilutes in water, releases this “citrate” in the solution?

Hi Kos, good question. Here we have the answer:
Citric acid (C6H8O7) also dissolves, donating an H+ to water to create a hydronium ion (H3O+(aq)) which is an acid.
The by-product of this reaction is citrate (C6H7O7-).
C6H8O7(aq) + H2O (l) → C6H7O7-(aq) + H3O+(aq)https://chem20cci.wikispaces.com/Help
Is this answering your question?

Thank you for your wishes Daniel!
Indeed citric acid has the safest profile of these “citrate” compounds…
Dr.Alberto, you treated a patient with primary peritoneal mesothelioma with citric acid , but you used much higher dose than usual…30gr/24h…why? It has to do with tumor resistance against citric acid, the location, the tumor mass?
In a patient with gastric adenocarcinoma with liver and peritoneum metastasis, what dosage do you suggest to use? Currently he is at 7gr/day.
Thank you.

1. I treated the patient with peritoneal mesothelioma on 2010, with 30-40 grams each day of citric acid, 5 months later a patient with ovarian cancer didn’t tolerate that amount of citric acid, so I told her to take only 5-7 grams of citric acid orally each day, and she get cured from cancer, then you know the history.. all the next patients only received 5-7 grams of citric acid orally each day… and I published some of them as this..

Dr Halabe,
Please , could you let me know if citric acid is toxic on liver when liver is really working badly? We are struggling with very serious radiation hepatitis. My husband has colon cancer with metastases to the liver. Since more than two months we are trying to get biliruibin down. It was 5 two weeks ago, now we are on cortison and one week ago it was 3.5. We have to get at least 2.5 to start on chemo. I am scared for the moment to do whatever, please advice if we need to wait with citric acid.

I know it is bad. Doctors say that they cannot do anything – just give cortisone and wait and see. If you have any directions for us, please let me know. And if you would use in that case citric acid or not. Nobody wants or is able to help us.

It’s difficult to say but I’m leaning towards “not extremely”. It’s quite possible that it is aiding in stability, or slowing growth. But I haven’t really seen shrinkage of any lesions systemically since I began taking it. Of course, I’m taking several other substances, including DCA and Metformin and others and I suppose the same thing can be said for them as well.

By “a number of months” I mean around 2 months probably and I’ve stopped treatment for a few weeks while undergoing TACE, as I’m not sure if it would interfere with the chemo. So it may not be a sufficient amount of time to say, as some of Dr. Halabe’s patients were on it for a number of months while seeing only modest responses – but still responses.

I can not say exactly. Ive got cyberknife after my tumor had relapse in march 2016. In june i started to get cytric acid (after reading this article) to prevent new relapse. In jule 2016 i did PET/CT. No traces of the tumor. And still no traces. Also Im taking metformin (500 + 500 mg) and mebendazole (100 + 100 mg) in morning and evening. Im taking cytric acid after omeprazole (20 mg) in the middle of day.

No, but it was the only change. Since May she is getting chemo and all the things what Daniel suggested. Her albumin was low until now. Her values were like this: 30,29,31,34,34,33,33,32,34,37 – first value on 4th of June then sample every fortnight. It is not a proof or statistically significant yet but if she hits 40 I will be convinced.

Thank you for updating us. I’m sorry to hear that it is back down slightly. I don’t know too much about albumin as a marker but to me it seems that it is staying within a relatively stable range after picking up initially from a bit of a lower range.

What I have learned albumin has an excellent prognostic value, seen studies calculating survival days from it. Wife’s CEA cancer marker went up from 13 to 36 at the same time – the highest ever for her.

Patients with cancer that only receive citric acid as their treatment get cured, as is described in my articles (that is called Scientific Methdo)… patients with cancer that receive many treatments, medical and alternative, and citric acid, get confused, and develop many complications related to those “treatments”… more than the complications of cancer…